Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function

Thioester-containing proteins (TEPs), which are distinguished by the thioester motif (GCGEQ), are essential to arthropods' defense against infections. Although TEPs have been extensively investigated in <i>Anopheles</i>, <i>Aedes</i>, and <i>Drosophila</i>, their functions in <i>Culex</i> mosquitoes remain inadequately explored. Interestingly, we discovered that <i>Culex</i> TEPs exhibit functional antagonism to their orthologs in other species, actively facilitating viral infection in this vector. In this study, we identified nine <i>TEP</i> genes in <i>Culex quinquefasciatus</i>, three of which were found to critically facilitate <i>Japanese encephalitis virus</i> (JEV) infection, with <i>CqTEP27</i> exhibiting the most pronounced proviral effect. Mechanistically, <i>Cq</i>TEP27 may have suppressed the production of several antimicrobial peptides (AMPs), which increased JEV replication. Our work also highlights the potential of targeting susceptibility factors such as <i>Cq</i>TEP27 to block pathogen acquisition. Notably, the rate of mosquito infection was significantly decreased by membrane blood feeding antisera against <i>Cq</i>TEP27. Therefore, vaccination against <i>Cq</i>TEP27 offers a workable method of avoiding JEV infection. According to our research, <i>Cq</i>TEP27 is a promising target for the development of vaccines that prevent JEV transmission. By preventing viral infection in mosquitoes that feed on immunized hosts, this approach can directly disrupt the natural transmission cycle, offering a novel strategy to reduce the disease burden.